HIV virology and immunology Flashcards

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1
Q

Describe the trend in CD4 count as time passes with HIV

A

CD4 count denies rapidly in the first 6 weeks, then rises slightly up tot 12 weeks and then decreases again gradually over several years in a period of clinical latency, reaching almost 0 after 10 years

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2
Q

Describe the trend in HIV RNA copies in the plasma

A

Increases rapidly for 6 weeks and then decreases till 12 weeks and then slowly rises up till for the next several years until about 7 years when the RNA copies rises dramatically causing first constitutional symptoms and then opportunistic infections and then death

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3
Q

What is the period of time called in the first few weeks after infection when the CD 4 count drops dramatically and the number of HIV RNA copies in the plasma increases dramatically?

A

Acute HIV syndrome - wide dissemination of the virus occurs

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4
Q

What is the period of time called when the CD 4 count is low but rising over several years?

A

clinical latency - asymptomatic stage

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5
Q

When is HIV very contagious?

A

in the first month post-infection as there is high viraemia. The individual is still asymptomatic at this stage
Also contagious during the latent period usually about 7 years (not on treatment) as they continue to have sex

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6
Q

What type of virus is HIV?

A

enveloped retrovirus

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7
Q

What is a retrovirus?

A

A virus that contains reverse transcriptase, so can convert its RNA into DNA and incorporate it into the host DNA

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8
Q

What are the characteristics of lentiviruses?

A

slow viruses

long incubation period

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9
Q

To what genus do HIV1 and 2 belong

A

Lentivirus

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10
Q

How did HIV arise?

A

transmission of SIV (simian) from chimpanzees to humans

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11
Q

What are the three HIV types?

A

M - main
O - outlying
N - new

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12
Q

list the 6 steps of viral replication generally

A
  1. attachment
  2. cell entry
  3. interaction with host cells
  4. replication
  5. assembly
  6. release
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13
Q

What is the attachment step of HIV replication?

A

HIV gp120 binds to CD4 on host cells

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14
Q

Describe the cell entry aspect of HIV replication

A

only the central viral core carrying the nucleic acid and some associated proteins enters the host cell

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15
Q

Describe how HIV interacts with host cells

A

HIV uses cell materials (enzymes, a.a. and nucleotides) for their replication
HIV subverts host cell defence mechanisms

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16
Q

Describe the release of HIV from cells

A

exocytosis from the cell over a period of time

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17
Q

What is the most abundant type of WBC?

A

neutrophils

18
Q

What do th1 cells do?

A

they produce specific interleukins (IL4,5,10,13) that cause maturation of B cells into plasma cells

19
Q

What do th2 cells do?

A

Th2 produce INF alpha and TNF, which activate CD 8 cells turning them into cytotoxic T cells and NK cells, which produce perforin to cause lysis of infected cells

20
Q

Which cytokine is important in the body’s response to TB?

A

INF alpha

21
Q

What does CD 4 do in the normal immune response?

A

orchestrates the immune response: eosinophils, neutrophils, NK cells, macrophages, B cells, CD 8 cells

22
Q

What is the problem with HIV activating CD 4 cells?

A

Activated CD 4 cells are destined to undergo activation induced cell death, leading to loss of CD 4 T cells

23
Q

List the mechanisms with which HIV affects the immune system and leads to acquired immune deficiency

A

Activated CD 4 cells are destined to undergo activation induced cell death, leading to loss of CD 4 T cells
bystander cell death - infected macrophage causes death of infected VD 4 T cell
Thymus atrophy - preventing thyme maturation of T ce;;s
loss of bone marrow progenitors
fibrosis of lymph nodes

24
Q

Describe the structure of HIV 1 **** listen to lec again

A
envelope
gp 120 and gp 41 on surface of envelope
matrix
capsid  containing p24
viral RNA and reverse transcriptase in core
25
Q

Describe the specific mechanism of HIV viral replication

A
  • BINDING: Glycoproteins on the HIV molecule (gP160 made of gP120 and gP 41) allow it to attach and fuse onto the CD4 and CCR5 receptors
  • ENTRY: The viral capsid then enters the cell and enzymes and nucleic acid are uncoated and released
  • INTERACTION IWTH HOST CELLS: Using reverse transcriptase single stranded RNA is converted into double stranded DNA
  • INTERACTION WITH HOST CELLS: Viral DNA then is integrated into the cells own DNA by integrase enzyme
  • REPLICATION: When the infected cell divides the viral DNA is read and transcibed and long chains of viral proteins are made
    ASSEMBLY: viral RNA is repackaged (spliced) and protein chains are cleaved and reassembled by the protease enzyme into individual proteins that combine to form a working virus
    RELEASE: Budding here immature virus pushes out of the cell taking with it some cell membrane
26
Q

What are the 9 steps of HIV replication?

A
Attachment
Entry
Uncoating
Reverse transcription (error prone so genomic variability)
Genome integration
Transcription of viral RNA
Splicing of mRNA and translation into proteins
Assembly of new virions
Budding
27
Q

How many genes does the RNA genome encode?

A

9

28
Q

Give some examples of proteins encoded by the RNA genes

A
envelope proteins
reverse transcriptase
integrase
protease
structural proteins
29
Q

list the cells infected by CD 4 - cell tropism

A
memory CD 4 cells 
naive CD 4 cells
macrophages - as have CD 4 and CCR5
dendritic cells 
brain microvascular endothelial cells 
bone marrow progenitor cells 
astrocytes 
renal epithelial cells
30
Q

Describe the initial infection of HIV

A
  1. virus enters via vaginal, rectal, intestinal mucosa
  2. local infection in one macrophage/dendritic cell that spreads to other cells
  3. these are APCs, so will go to the local lymph node and present antigen to T cells
  4. infection of T cells
  5. T cells leave the lymph node and infection reaches the bloodstream
  6. exponential rise in T cell infection
31
Q

What are the two initial methods used by the immune system to get rid of HIV?

A

humoral

cell-mediated

32
Q

What is the humeral response to HIV?

A

neutralising Abs produced

33
Q

What are the problems of the humeral response to HIV?

A

neutralising antibodies are of a low magnitude (size of response low)
envelope glycoprotein is poorly immunogenic
envelope glycoprotein shows genetic diversity - mutations

34
Q

What is the cell mediated response to HIV?

A

CD 8 and CD 4 cells

35
Q

What are the problems with the cell mediated response to HIV?

A
  • CD 8 cells are incomplete as the viral antigens keep changing, so virus escapes
    so the CTL response is quantitatively and qualitatively poor
  • poor CD 4 response and failure of proliferation of CD 4 cells
  • excessive activation of CD 4 cells
  • decreased proliferation of CD 4 cells with antigens
  • impaired production of IL-2 and IL2 - R
  • preferential involvement of memory T cells
  • decline in number and function of CD 4 cells
36
Q

Why is it difficult to make a vaccine for HIV?

A

difficult to find a protective immune response

37
Q

What is the name given to people who don’t progress to AIDS?

A

long term non-progressors

38
Q

Why is it through that some people don’t progress to AIDS - what are their characteristics?

A

genetic factors in CCR5

vigorous CTL responses as they may have differences in MHC I

39
Q

list ways in which the CD4 count decreases

A
direct cytotoxicity
impaired cell homeostasis
syncytial formation
apoptosis
bystander cell killing  - immune cells kill other immune cells 
decreased production
infection of progenitors in bone marrow
infection of thymocyte progenitors and thymus atrophy
redistribution
40
Q

In what areas can HIV hide from the immune system?

A

genital tract
CNS
GI
bone marrow